Saliva does far more than wet your mouth. It helps digest starch, shields teeth, and fends off germs.
A new genomic deep dive shows that saliva itself has been evolving quickly, especially in primates, through gene duplications, losses, and regulatory tweaks.
That rapid churn likely tracks shifts in diet and disease pressure over millions of years.
The primate twist on saliva
Researchers at the University at Buffalo compared DNA and RNA across species and found that secretory calcium-binding phosphoprotein (SCPP) genes expanded and shifted at key evolutionary moments.
Early animals building skeletons, fishes laying down enamel, and mammals producing milk all left signatures at this locus. The same region now encodes many of the abundant proteins from our teeth.
“Our work highlights how evolutionary adaptations to diet and disease may have influenced primate biology, including humans,” explained Stefan Ruhl, who has spent years mapping saliva’s biology.
Rapid evolution of saliva
The team started from a simple idea: a fluid constantly exposed to food and microbes should be under strong, changeable selection.
“Our idea was that saliva, as a biological fluid that constantly interacts with food, microbes, and pathogens, may evolve more rapidly than other systems,” said Omer Gokcumen, an evolutionary anthropologist.
The team’s comparative analysis supported the theory. The genes that make our most abundant salivary proteins have duplicated, diverged, and been rewired repeatedly in the primate lineage.
That turnover helps explain why human saliva doesn’t look like a carbon copy of our ape cousins’, despite our close genetic kinship.
Not just like apes
The surprise landed when the group lined up human saliva against great apes.
“If you look at their blood, it’s pretty identical to ours in its composition. We thought it would be the same for saliva, with maybe one or two different components we could study,” Ruhl said.
“How wrong we were. It turned out there were not one or two but many substances that were different.”
Those differences make functional sense. Nonhuman primates carry relatively little salivary amylase, the enzyme that clips starch into sugars. Humans carry a lot.
That shift aligns with our long history of eating starchy roots, grains, and tubers.
Why abundant proteins matter
Most of the 3,000-plus molecules detectable in saliva are bit players. A small handful dominate, and those gland-made proteins do the heavy lifting for oral health.
“We know that saliva contains almost everything that also appears in blood,” Ruhl said. “Those abundant proteins, produced by the salivary glands, are probably the ones that really matter for keeping the mouth healthy because the salivary glands have evolved to protect the teeth.”
“Teeth are the only place in the body where a mineralized substance is exposed to the environment. And it’s constantly being challenged by acids from food and those produced by bacteria that cause dental caries, along with the simple mechanical attrition of chewing.”
Intriguingly, several of the genes behind those abundant proteins sit in the same neighborhood as milk caseins, which deliver calcium to infants. Milk supports bones, while saliva helps remineralize and protect enamel.
The influence of diet
The pattern extends across species and food niches. “We have proven that saliva protein composition is influenced by diet,” Ruhl said.
“The environment a certain animal lives in and what it prefers to consume will shape, evolutionarily speaking, the composition of saliva proteins.”
“The real development of the saliva genes that resemble those in humans occurred in the primate lineage. That was interesting to us because nonhuman primates are picky eaters, and they mostly choose from a variety of fruit and veggies.”
Ruhl said his team believes that the diversity of saliva proteins in primates must have something to do with them being able to distinguish between different taste varieties or to protect them from harmful substances in the plants they eat.
“We know that bats are very diverse in their diets. There are some that eat fruit, some that eat insects, and some that suck blood,” noted Ruhl.
“It would be interesting to study their salivary composition. I would predict that a similar diversification of saliva proteins evolved as in primates.”
Saliva as a diagnostic fluid
These insights aren’t just a biology curiosity. They point toward practical diagnostics and care.
If saliva evolves quickly with diet and environment, baseline “normal” may vary across populations and cultures, and will be shaped by what people eat, where they live, and their genetic backgrounds.
“If you want to find reliable biomarkers for disease and disorders, you first have to establish a robust baseline,” Ruhl said.
“We know there are biomarkers among different individuals, but we don’t know what their normal baseline levels in saliva are, whether it has to do with our genetic backgrounds or where and how we live and eat.”
He argues that dentistry should routinely claim saliva as its primary diagnostic fluid, the way medicine relies on blood and urine.
What rapid evolution means for risk
Genes that change fast can create weak spots as well as strengths. Some variants that were once helpful for a particular diet or pathogen load might raise risk for cavities, erosion, or even systemic issues under modern conditions.
“This could be cavities or metabolic variation, under particular environmental circumstances. In that sense, our results open the door to exploring personalized medicine approaches related to oral and systemic health,” said Ruhl.
“More broadly, the study provides new insight into how novel genes can emerge and diversify across species.”
The study is published in the journal Genome Biology and Evolution.
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